The further design, study, and bioanalytical applications of novel polymer membrane based chemical sensors are proposed. This research will build upon the recent successes of this program in developing a variety of new ion/gas chemical sensors that are useful for the direct detection of biomedically important species in complex samples, including whole blood. Efforts during the next phase of this project will include both fundamental and applied studies, with an emphasis on pursuing completely new concepts/strategies, both with respect the type analyte ions that may be detected via polymer membrane technology, and the chemical methods used to achieve desired ion selectively. A major thrust of the program will be to identify and study highly selective membrane chemistries for in situ sensing of anionic species. Specific new goals include: 1) examining the response mechanism and potential bioanalytical applications of a novel polymer membrane electrode that exhibits unique and clinically useful potentiometric response to the anticoagulant heparin, a macromolecular polyanion (both porcine and beef types); 2) studying the response properties/mechanisms of metalloporphyrin base anion-selective membranes with focus on determining the theoretical and practical advantages of adding fixed lipophilic anionic sites to enhance anion selectivity and on developing a Co(III)-porphyrin or corrin based nitrite selective sensors for monitoring cellular activity of nitric oxide synthase; and 3) assessing the utility of new molecular/ion imprinting techniques to prepare polymer films (silicone rubber) that may exhibit enhanced potentiometric selectivity to biologically important anions, especially carbonate, phosphates, low molecular weight heparin fragments, etc. In addition to these new directions, ongoing efforts to use various surface modification methods to render polymer membrane types gas and ion-selective catheter type sensors more blood compatible will be extended into this next phase of support. It is anticipated that this research program will continue to provide the biomedical community with an array of new/or improved chemical sensors as well the basic knowledge and chemistry that will be required to develop additional sensors, both electrochemical and optical, in the future.